Corcept's ALS Drug Shows Mixed Results: Survival Benefit Despite Missed Endpoint

Corcept Therapeutics has reported mixed results from its Phase II trial of dazucorilant, an investigational cortisol modulator for the treatment of amyotrophic lateral sclerosis (ALS). While the drug failed to meet its primary endpoint of improving functional performance, exploratory analyses revealed a significant survival benefit, sparking discussions about the potential path forward for the treatment.

Primary Endpoint Missed, But Survival Data Promising

The Phase II study, which enrolled 249 patients across the United States, Canada, and Europe, failed to demonstrate a statistically significant improvement in the ALS Functional Rating Scale-Revised (ALSFRS-R) scores compared to placebo. This scale evaluates patients' disability and respiratory function, among other metrics.

However, an exploratory analysis of the data presented at the 2025 annual meeting of the European Network to Cure ALS showed a marked improvement in overall survival. At the 24-week mark, none of the 83 patients in the 300 mg dazucorilant arm had died, compared to five deaths out of 82 patients in the placebo group. Extended analysis at one year revealed that treatment with dazucorilant reduced the risk of death by 84% versus placebo.

Bill Guyer, Corcept's Chief Development Officer, emphasized the urgent need for life-extending medications in ALS, stating, "We are working with regulatory authorities to determine the optimal path for advancing dazucorilant."

Safety Profile and Gastrointestinal Concerns

The safety profile of dazucorilant has raised some concerns among analysts. Truist Securities noted increased gastrointestinal adverse events in patients receiving the drug. The 300 mg dazucorilant group experienced a higher rate of severe treatment-emergent adverse events (19%) compared to the placebo group (13%).

Despite these concerns, Corcept maintains that dazucorilant demonstrated "an acceptable safety profile," with 92% of adverse events classified as mild to moderate in severity. No deaths related to treatment-emergent adverse events were reported in the 300 mg group, compared to four in the placebo group.

Implications for Corcept and Future Developments

While the ALS trial results present a complex picture, analysts at Truist Securities consider the readout to be only "incremental" to Corcept's overall stock narrative. The firm does not include dazucorilant in its valuation of the biotech company.

Corcept is currently engaging with regulatory authorities to determine the best path forward for dazucorilant in ALS treatment. The company's stock saw a modest increase of 1.4% in premarket trading following the announcement, with a market capitalization of $7.4 billion.

As the pharmaceutical industry continues to seek effective treatments for ALS, Corcept's mixed results highlight the challenges and potential breakthroughs in this critical area of research. The company's next steps with dazucorilant will be closely watched by patients, clinicians, and investors alike.